TY - JOUR
T1 - Analyses of HIV-1 drug-resistance profiles among infected adolescents experiencing delayed antiretroviral treatment switch after initial nonsuppressive highly active antiretroviral therapy
AU - Agwu, Allison
AU - Lindsey, Jane C.
AU - Ferguson, Kimberly
AU - Zhang, Haili
AU - Spector, Stephen
AU - Rudy, Bret J.
AU - Ray, Stuart C.
AU - Douglas, Steven D.
AU - Flynn, Patricia M.
AU - Persaud, Deborah
PY - 2008/7/1
Y1 - 2008/7/1
N2 - Treatment failure and drug resistance create obstacles to long-term management of HIV-1 infection. Nearly 60% of infected persons fail their first highly active antiretroviral therapy (HAART) regimen, partially because of nonadherence, requiring a switch to a second regimen to prevent drug resistance. Among HIV-infected youth, a group with rising infection rates, treatment switch is often delayed; virologic and immunologic consequences of this delay are unknown. We conducted a retrospective, longitudinal study of drug resistance outcomes of initial HAART in U.S. youth enrolled between 1999-2001 in a multicenter, observational study and experiencing delayed switch in their first nonsuppressive treatment regimen for up to 3 years. HIV-1 genotyping was performed on plasma samples collected longitudinally, and changes in drug resistance mutations, CD4+ T cell numbers and viral replication capacity were assessed. Forty-four percent (n = 18) of youth in the parent study experiencing virologic nonsuppression were maintained on their initial HAART regimen for a median of 144 weeks. Drug resistance was detected in 61% (11/18) of subjects during the study. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (8/10) drug resistance mutations than those on protease-inhibitor (PI) regimens (2/7) (p = 0.058). Subjects developing NNRTI-resistance (NNRTI-R), showed a trend toward lower CD4+ T cell gains (median: -6 cells/mm3 per year) than those without detectable NNRTI-R (median: +149 cells/mm3 per year) (p = 0.16). HIV-1-infected youth maintained on initial nonsuppressive NNRTI-based HAART regimens are more likely to develop drug-resistant viremia than with PI-based HAART. This finding may have implications for initial treatment regimens and transmission risk in HIV-infected youth, a group with rising infection rates.
AB - Treatment failure and drug resistance create obstacles to long-term management of HIV-1 infection. Nearly 60% of infected persons fail their first highly active antiretroviral therapy (HAART) regimen, partially because of nonadherence, requiring a switch to a second regimen to prevent drug resistance. Among HIV-infected youth, a group with rising infection rates, treatment switch is often delayed; virologic and immunologic consequences of this delay are unknown. We conducted a retrospective, longitudinal study of drug resistance outcomes of initial HAART in U.S. youth enrolled between 1999-2001 in a multicenter, observational study and experiencing delayed switch in their first nonsuppressive treatment regimen for up to 3 years. HIV-1 genotyping was performed on plasma samples collected longitudinally, and changes in drug resistance mutations, CD4+ T cell numbers and viral replication capacity were assessed. Forty-four percent (n = 18) of youth in the parent study experiencing virologic nonsuppression were maintained on their initial HAART regimen for a median of 144 weeks. Drug resistance was detected in 61% (11/18) of subjects during the study. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (8/10) drug resistance mutations than those on protease-inhibitor (PI) regimens (2/7) (p = 0.058). Subjects developing NNRTI-resistance (NNRTI-R), showed a trend toward lower CD4+ T cell gains (median: -6 cells/mm3 per year) than those without detectable NNRTI-R (median: +149 cells/mm3 per year) (p = 0.16). HIV-1-infected youth maintained on initial nonsuppressive NNRTI-based HAART regimens are more likely to develop drug-resistant viremia than with PI-based HAART. This finding may have implications for initial treatment regimens and transmission risk in HIV-infected youth, a group with rising infection rates.
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U2 - 10.1089/apc.2007.0200
DO - 10.1089/apc.2007.0200
M3 - Article
C2 - 18479228
AN - SCOPUS:47849105010
SN - 1087-2914
VL - 22
SP - 545
EP - 552
JO - AIDS patient care and STDs
JF - AIDS patient care and STDs
IS - 7
ER -